The excitatory amino acids, glutamate and aspartate have been porposed as transmitters in the central nervous system. At present, we know little of the mechanisms operative at central excitatory synapses, but acquisition and exploitation of such knowledge would undoubtedly lead to advances in the diagnosis and therapy of behavioral and neurological dysfunction. To this end, a series of studies is proposed to characterize the mechanisms used by synapses at which glutamate and aspartate serve as transmitters. Strong evidence suggests that these amino acids mediate transmission at well-defined synapses in the rat hippocampal formation, and these will serve as models for the proposed studies. Binding sites for excitatory amino acids on hippocampal synaptic membranes will be identified and characterized. Their role as postsynaptic receptors will be evaluated by physiological and pharmacological comparisons with the receptors activated in hippocampal slices by stimulation of the appropriate pathways or by bath application of amino acids. Finally, the control of glutamate and aspartate release processes will be examined, particularly the sources of the releasable store and the involvement of presynaptic receptors. These studies, in addition to advancing our understanding of excitatory transmission in the central nervous system, will also be of behavioral interest, since the hippocampal synapses chosen for these studies show forms of physiological plasticity that are considered to represent the simplest components of behavior.